Chemical characterization of a family of brain lipids that induce sleep
Abstract
A molecule isolated from the cerebrospinal fluid of sleep-deprived cats has been chemically characterized and identified as cis-9,10-octadecenoamide. Other fatty acid primary amides in addition to cis-9,10-octadecenoamide were identified as natural constituents of the cerebrospinal fluid of cat, rat, and human, indicating that these compounds compose a distinct family of brain lipids. Synthetic cis-9,10-octadecenoamide induced physiological sleep when injected into rats. Together, these results suggest that fatty acid primary amides may represent a previously unrecognized class of biological signaling molecules.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
AEA is actively degraded by the serine hydrolase enzyme FAAH.
“the ECB N-arachidonoylethanolamide (anandamide, AEA) is actively degraded by the serine hydrolase enzyme, fatty acid amide hydrolase (FAAH).”
From Amygdala FAAH and anandamide: mediating protection and recovery from stress (2013) · cites this paper as [44]
Cites
Isolation and Structure of a Brain Constituent That Binds to the Cannabinoid Receptor
Devane, W. A., Hanuš, L., Breuer, A., Pertwee, R. G., Stevenson, L. A., Griffin, G., Gibson, D., Mandelbaum, A., Etinger, A., & Mechoulam, R. (1992) · Science · doi:10.1126/science.1470919 · Cited by 5,633 · see citing works
The Biosynthesis of Neuropeptides: Peptide alpha-Amidation
Eipper, B. A., Stoffers, D. A., & Mains, R. E. (1992) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.15.030192.000421 · Cited by 610 · see citing works
The Biosynthesis Of Neuropeptides: Peptide Alpha-Amidation
Eipper, B. A. (1992) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.15.1.57 · Cited by 489 · see citing works
Devane, W. A., & Axelrod, J. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.14.6698 · Cited by 220 · see citing works
Prostaglandin D2 induces sleep when microinjected into the preoptic area of conscious rats
Ueno, R., Ishikawa, Y., Nakayama, T., & Hayaishi, O. (1982) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(82)91760-0 · Cited by 172 · see citing works
Cerebrodiene: a brain lipid isolated from sleep-deprived cats.
Lerner, R. A., Siuzdak, G. E., Prospero-Garcia, O. E., Henriksen, S. J., Boger, D. L., & Cravatt, B. F. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.20.9505 · Cited by 110 · see citing works
Self-citationIdentification of fatty acid amides in human plasma
Arafat, E. S., Trimble, J. W., Andersen, R. N., Dass, C., & Desiderio, D. M. (1989) · Life Sciences · doi:10.1016/0024-3205(89)90278-6 · Cited by 85 · see citing works
Isolation of fatty acid amide as an angiogenic principle from bovine mesentery
Wakamatsu, K., Masaki, T., Itoh, F., et al. (1990) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(90)92338-z · Cited by 79 · see citing works
Jain, M. K., Ghomashchi, F., Yu, B.-Z., et al. (1992) · Journal of Medicinal Chemistry · doi:10.1021/jm00097a018 · Cited by 52 · see citing works
Characterization, Properties and Multivariate Functions of Delta-Sleep-Inducing Peptide (DSIP)
Schoenenberger, G. A. (2008) · European Neurology · doi:10.1159/000115711 · Cited by 43 · see citing works
Determination of the structure of unsaturated fatty acids via degradative methods
Privett, O. S. (1971) · Progress in the Chemistry of Fats and other Lipids · doi:10.1016/0079-6832(71)90025-5 · Cited by 33 · see citing works
Pharmacology of ethanol and glutamate antagonists on rodent sleep: A comparative study
Prospero-Garcia, O. E., Criado, J., & Henriksen, S. J. (1994) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(94)90442-1 · Cited by 29 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides
Cravatt, B. F., Giang, D. K., Mayfield, S. P., Boger, D. L., Lerner, R. A., & Gilula, N. B. (1996) · Nature · doi:10.1038/384083a0 · Cited by 2,125 · see citing works
Self-citationThe Endocannabinoid System as an Emerging Target of Pharmacotherapy
Pacher, P., Bátkai, S., & Kunos, G. (2006) · Pharmacological Reviews · doi:10.1124/pr.58.3.2 · Cited by 2,077 · see citing works
Cravatt, B. F., Demarest, K., Patricelli, M. P., Bracey, M. H., Giang, D. K., Martin, B. R., & Lichtman, A. H. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.161191698 · Cited by 1,310 · see citing works
Self-citationIdentification of bioactive metabolites using activity metabolomics
Rinschen, M. M., Ivanisevic, J., Giera, M., & Siuzdak, G. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0108-4 · Cited by 1,008 · see citing works
Self-citationStructure and function of fatty acid amide hydrolase
McKinney, M. K., & Cravatt, B. F. (2005) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.74.082803.133450 · Cited by 680 · see citing works
Self-citationEnzymatic pathways that regulate endocannabinoid signaling in the nervous system
Ahn, K., McKinney, M. K., & Cravatt, B. F. (2008) · Chemical Reviews · doi:10.1021/cr0782067 · Cited by 529 · see citing works
Self-citationNew insights into copper monooxygenases and peptide amidation: Structure, mechanism and function
Prigge, S. T., Mains, R. E., Eipper, B. A., & Amzel* **, L. M. (2000) · Cellular and Molecular Life Sciences · doi:10.1007/pl00000763 · Cited by 460 · see citing works
Egertová, M., Cravatt, B. F., & Elphick, M. R. (2003) · Neuroscience · doi:10.1016/s0306-4522(03)00145-3 · Cited by 347 · see citing works
Self-citationBiochemical regulation of non-rapid-eye-movement sleep
Krueger, J. M. (2003) · Frontiers in Bioscience · doi:10.2741/1033 · Cited by 329 · see citing works
Chemical Probes of Endocannabinoid Metabolism
Blankman, J. L., & Cravatt, B. F. (2013) · Pharmacological Reviews · doi:10.1124/pr.112.006387 · Cited by 327 · see citing works
Self-citationLichtman, A. H., Shelton, C. C., Advani, T., & Cravatt, B. F. (2004) · Pain · doi:10.1016/j.pain.2004.01.022 · Cited by 301 · see citing works
Self-citationChiang, K. P. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh216 · Cited by 278 · see citing works
Circuitry for associative plasticity in the amygdala involves endocannabinoid signaling
Azad, S. C., Monory, K., Marsicano, G., Cravatt, B. F., Lutz, B., Zieglgänsberger, W., & Rammes, G. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.2134-04.2004 · Cited by 263 · see citing works
Tsou, K., Nogueron, M. I., Muthian, S., Sañudo-Peña, M. C., Hillard, C. J., Deutsch, D. G., & Walker, J. M. (1998) · Neuroscience Letters · doi:10.1016/s0304-3940(98)00700-9 · Cited by 240 · see citing works
Amygdala FAAH and anandamide: mediating protection and recovery from stress
Gunduz-Cinar, O., Hill, M. N., McEwen, B. S., & Holmes, A. (2013) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2013.08.008 · Cited by 229 · see citing works
Juszczak, G. R., & Swiergiel, A. H. (2009) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2008.12.014 · Cited by 211 · see citing works
The endogenous cannabinoid system and its role in nociceptive behavior
Cravatt, B. F., & Lichtman, A. H. (2004) · Journal of Neurobiology · doi:10.1002/neu.20080 · Cited by 203 · see citing works
Evaluation of fatty acid amide hydrolase inhibition in murine models of emotionality
Naidu, P. S., Varvel, S. A., Ahn, K., Cravatt, B. F., Martin, B. R., & Lichtman, A. H. (2007) · Psychopharmacology · doi:10.1007/s00213-006-0689-4 · Cited by 184 · see citing works
Self-citationLitjens, M. J. J., Straathof, A. J. J., Jongejan, J. A., & Heijnen, J. J. (1999) · Tetrahedron · doi:10.1016/s0040-4020(99)00724-3 · Cited by 42 · see citing works
Cannabinoid receptor systems: therapeutic targets for tumour intervention.
Jones, S., & Howl, J. (2003) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.7.6.749 · Cited by 13 · see citing works
- Authors
- Cravatt, B. F., Prospero-Garcia, O., Siuzdak, G., Gilula, N. B., Henriksen, S. J., Boger, D. L., & Lerner, R. A.
- Affiliations
- Scripps Research Institute (US)
- Venue
- Science
- Published
- 1995-06-09
- Volume
- 268
- Issue
- 5216
- Pages
- 1506-1509
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2042544913
- Cited by
- 620
- References
- 12
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 8 · 2023: 19 · 2022: 17 · 2021: 20 · 2020: 12 · 2019: 12 · 2018: 24 · 2017: 10 · 2016: 13 · 2015: 11 · 2014: 18 · 2013: 22 · 2012: 17
- FWCI
- 17.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1s10rr007273-01)
- National Institute on Drug Abuse (R01DA015648)
- National Center for Research Resources (1 S10 RR07273-01)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Keywords
- sleep induction, cerebrospinal fluid, brain lipids, sleep deprivation, cats, rats, human
- MeSH terms
- Animals, Brain Chemistry, Cats, Cerebrosides, Humans, Lipids, Molecular Weight, Magnetic Resonance Spectroscopy, Oleic Acids, Sleep, Spectrophotometry, Infrared, Mass Spectrometry, Signal Transduction, Spectrometry, Mass, Fast Atom Bombardment, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
